PROJECT SUMMARY/ABSTRACT Substance use and condomless same-sex are two predominant modes of HIV transmission in the Philippines, where one of the world?s fastest growing epidemics is taking place. Clans of transgender women (TW) and men who have sex with men (MSM) are highly impacted and account for four-fifths (80%) of new cases per year. However, coverage of HIV prevention (HIV-P) and harm reduction services (e.g., HIV testing, condoms, Pre- and non-occupational Post-Exposure Prophylaxes, and needle and syringe exchange programs) in the Philippines is sub-par, with only a-third of TW and MSM individuals being reached by HIV-P programs. This low uptake of HIV-P services partially stems from the currently limited research in this context and setting, as well as the underexplored social and cultural factors such as ?clan memberships? and clan activities that could be facilitate protective factors (e.g., social support, sharing of HIV/drug-related information) as well as risk (e.g., inconsistent condom use, and sex with multiple partners across and within clan members), and multiple structural policies and healthcare-related barriers that impact uptake of HIV-P and harm reduction services. To fill in this gap in HIV prevention and lay the groundwork for future studies in the Philippines, the current dissertation proposal builds on my formative, community-informed qualitative research, and aims to characterize substance use, co-occurring HIV-risk behaviors, and uptake of HIV-P services on a sample of sexually active, HIV-negative TW and MSM clan members who are living in Manila. Specifically, this study will use an integrated Socio-Ecological Model and Situated Information-Motivation-Behavioral skills Model, with principles based on community-informed research, to (1) assess via multiple regression and structural equational modeling the substance use, HIV-risk behaviors, and other multi-level socio-ecological risk and predictors of uptake of HIV-P services using secondary data from Project Lakambini, the largest online survey of Filipina/o TW and MSM clans in Manila to date (n=300, 35% self-identifying as TW); and (2) qualitatively identify and characterize via Pagkikipagkwentuhan (story sharing), an indigenous Filipino qualitative method, to situate the context of TW and MSM clan members? substance use-related informational knowledge, motivations, and behavioral skills (IMB) across social, personal, and structural factors that impact uptake of HIV-P services within and across of Filipina/o clans members through 4 focus groups (5-8 participants per group; approx. 16 TW and 16 MSM clan members). The study results will provide evidence for the kinds of social context-specific (e.g, clan memberships) risk and protective factors that influence this important behavioral outcome (i.e., uptake of HIV-P services) in preventing HIV infection among clans of TW and MSM in Manila. A better understanding of how to improve uptake of HIV-P services can help inform national public health efforts in designing ongoing and future HIV prevention and substance use-related harm reduction programs.